The purpose of this application is to apply a novel ethno-spatial approach to evaluate the impact of social, structural, and environmental factors on HIV risk behavior, HIV incidence, and HIV treatment outcomes among illicit drug users (DU) and female sex workers (FSW). As well, we seek to explore critical initiation and transition events that shape risk trajectories within these populations. Our proposed study is nested within a larger program of research that includes five NIDA-funded longitudinal cohort studies of adult DU and FSW and street-involved youth in Vancouver, Canada. Thus, our approach offers a 'value-added' opportunity to employ and integrate multiple data collection and analytic techniques to identify the impacts of social, structural and physical features of sex work and drug use scenes on HIV outcomes, and will include ethnographic observational fieldwork, in- depth interviews, geo-spatial mapping techniques, and quantitative laboratory and survey data. Through this effort we will seek to advance methodological approaches to the study of HIV/AIDS among vulnerable populations, by piloting a novel ethno-spatial approach to elucidate the complex pathways to HIV risk and HIV treatment among DU and FSW. Further, we aim to create a platform for the ongoing ethno-spatial evaluation of future interventions targeting DU and FSW that can be replicated in other settings within North America. The city of Vancouver is an ideal setting for the proposed research. Like many cities in the US, Vancouver is home to established drug and sex work scenes, and has experienced a high burden of HIV infection among DU and FSW. Officials in Vancouver, like those in several US municipalities, are implementing a range of policies and interventions aimed at reducing the public health and public order impacts of drug use and sex work, including those involving policing, supportive housing, and modifications to the physical environment. A nascent body of evidence suggests that while these interventions can reduce public disorder, they often have unintended negative consequences for vulnerable populations, prompting calls for an integration of public health and public order initiatives. However, the impact of such interventions on HIV risk behavior, HIV incidence, and HIV treatment outcomes has not been fully elucidated. Likewise, the associated impacts on critical initiation and transitional events among DU and FSW that shape risk trajectories are not well understood. Globally, there is growing recognition of the need to identif how social, structural and physical environments affect the health of marginalized drug using populations, and how interventions can address these levels of influence. The evaluation of social and structural influences and the promotion of methodological diversity have been identified as high priorities within the Office of AIDS Research's Trans-NIH Plan for 2011. Accordingly, through the use of complementary and innovative mixed-methods research, we aim to address several urgent health challenges, which will inform the development of a range of policies and interventions in both Canada and the United States.